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Identification of a novel compound that inhibits both mitochondria-mediated necrosis and apoptosis

Satoko Arakawa1, Ikuko Nakanomyo1, Yoko Kudo-Sakamoto2

  • 1Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

Biochemical and Biophysical Research Communications
|October 13, 2015
PubMed

Insights

Researchers screened for compounds inhibiting both apoptosis and necrosis. They found TMD#7538, which blocks mitochondrial outer membrane permeabilization (MOMP) and permeability transition pore (PTP) opening, suppressing cell death.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Pathological cell death, including apoptosis and necrosis, is crucial in various diseases.
  • Mitochondrial outer membrane permeabilization (MOMP) and permeability transition pore (PTP) opening are key mechanisms inducing these cell death pathways.
  • Oxygen radical-mediated cell injury often involves these mitochondrial events.

Purpose of the Study:

  • To identify small compounds capable of inhibiting both MOMP-mediated apoptosis and PTP-mediated necrosis.
  • To find novel therapeutic agents for pathological conditions involving cell death.

Main Methods:

  • Mitochondria-based high-throughput screening of a chemical library.
  • Assay development to detect MOMP and PTP opening.
  • Cell death assays using H2O2-induced injury in mouse embryonic fibroblasts and rat neonatal cardiomyocytes.

Main Results:

  • A novel small compound, TMD#7538, was identified.
  • TMD#7538 effectively inhibits both MOMP and PTP opening.
  • TMD#7538 suppressed H2O2-induced apoptosis and necrosis in tested cell types.

Conclusions:

  • TMD#7538 is a potent inhibitor of key mitochondrial cell death pathways.
  • This compound demonstrates potential therapeutic value in mitigating cell injury associated with apoptosis and necrosis.
  • Targeting mitochondrial membrane permeability offers a promising strategy for treating oxidative stress-related pathologies.
Keywords:
ApoptosisMOMPNecrosisPTPSmall compound

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